Central nervous system (CNS) metastasis is the most common intracranial tumor, and has a yearly incidence of over 170,000 new cases in the United States (Al-Shamy G, Sawaya R. Management of brain metastases: the indispensable role of surgery. J Neurooncol 2009; 92(3):275-82). The incidence of CNS metastasis has increased in recent years, possibly due to prolonged survival of patients given aggressive treatments for their primary disease. Lung and breast cancers are the most common types of primary tumors to develop brain metastases. Brain metastases are present in approximately 10-16% of patients with metastatic disease but large autopsy studies indicate frequencies as high as 18-45% (Al-Shamy G, Sawaya R. Management of brain metastases: the indispensable role of surgery. J Neurooncol 2009; 92(3):275-82; Weil R J, Palmieri D C, Bronder J L, Stark A M, Steeg P S. Breast cancer metastasis to the central nervous system. Am J Pathol 2005; 167(4):913-20; and Sharma M, Abraham J. CNS metastasis in primary breast cancer. Expert Rev Anticancer Ther 2007; 7(11):1561-6). CNS metastases occur rapidly, usually within 2-3 years following diagnosis of metastatic disease, and the median survival from detection of CNS involvement is a stifling 13 months (Al-Shamy G, Sawaya R. Management of brain metastases: the indispensable role of surgery. J Neurooncol 2009; 92(3):275-82).
Metastasis to the CNS remains a major cause of morbidity and mortality in patients with systemic cancers and is a common sanctuary site for patients with breast or lung cancer metastasis. Brain metastases are becoming increasingly prevalent as greater control over systemic disease is achieved. There have been limited improvements in the treatment of brain metastases and current treatment paradigms rely on surgical resection and radiation therapy.
Progress in treating brain metastases has been hampered by a lack of model systems, a lack of human tissue samples, and the exclusion of brain metastatic patients from many clinical trials. Current models are principally derived from cell lines and likely do not represent the human disease. Moreover, there are relatively few therapeutic options for brain/central nervous system metastases beyond surgery and radiation because of the metastases multi-focal nature and association with late-stage disease and other distant manifestations. As such, there is a need to work toward innovative treatment approaches for patients with CNS metastasis and metastases to other locales within the body. The development of preclinical models will be critical for the development of novel therapies and a better understanding of the disease biology. Moreover, the development of preclinical models could have provide useful information regarding predictive biomarkers, preventative measures, and “end-point” therapies.